Synthesis of sterically hindered phenolic compounds from indole and its derivatives

Article abstract of DOI:10.1134/S1070428007120093

Reactions of 3,5-di-tert-butyl-4-hydroxybenzyl acetate with indole and its derivatives gave a series of sterically hindered phenolic compounds having various functional groups. The products are potentially capable of inhibiting radical chain oxidation processes according to different mechanisms.

Full text of DOI:10.1134/S1070428007120093

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 12, pp. 1797–1803. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © G.N. Nugumanova, S.V. Bukharov, R.G. Tagasheva, M.V. Kurapova, V.V. Syakaev, N.A. Mukmeneva, P.A. Gurevich, A.R. Burilov,
2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1796–1801.
Synthesis of Sterically Hindered Phenolic Compounds
from Indole and Its Derivatives
G. N. Nugumanovaa, S. V. Bukharova, R. G. Tagashevaa, M. V. Kurapovaa, V. V. Syakaevb,
N. A. Mukmenevaa, P. A. Gurevicha, and A. R. Burilovb
a Kazan State University of Technology, ul. K. Marksa 68, Kazan, 420015 Tatarstan, Russia
e-mail: guliang1@rambler.ru
b Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
Received March 20, 2007
Abstract—Reactions of 3,5-di-tert-butyl-4-hydroxybenzyl acetate with indole and its derivatives gave a series
of sterically hindered phenolic compounds having various functional groups. The products are potentially
capable of inhibiting radical chain oxidation processes according to different mechanisms.
DOI: 10.1134/S1070428007120093
Design of effective polyfunctional stabilizers char-
acterized by internal synergism [1] is a promising line
in the field of stabilization of organic media and poly-
meric materials. Interest in sterically hindered phenolic
compounds based on indole and its derivatives is
related to the possibility of obtaining such polyfunc-
tional stabilizers. Indole derivatives themselves are
known as light and heat stabilizers for poly(vinyl
chloride) and other chlorine-containing polymers [2];
introduction of sterically hindered phenolic fragments
could give rise to additional antioxidant properties.
Some indole derivatives such as substituted isatins (in
particular, N-methylisatin 3-thiosemicarbazone) are
known as medical agents [3]. Sterically hindered
phenols also constitute structural fragments of a num-
ber of drugs [4]. Therefore, compounds derived from
indole and sterically hindered phenols may be prom-
ising from the viewpoint of biological activity.
of indole (I) or isatin (II) with 2,6-di-tert-butylphenol
(III) and formaldehyde were unsuccessful. The reac-
tion with indole in the presence of an acid catalyst
resulted in the formation of unidentified compounds,
presumably as a result of indole condensation. When
a solution of isatin (II), phenol III, and formaldehyde
in alcohol was heated for 15 h under reflux, only 7%
of 1-(3,5-di-tert-butyl-4-hydroxybenzyl)-2,3-dihydro-
1H-indole-2,3-dione (IV) was formed (according to
the 1H NMR data; Scheme 1).
3,5-Di-tert-butyl-4-hydroxybenzyl acetate (V) is an
effective benzylating agent which ensures introduction
of 3,5-di-tert-butyl-4-hydroxybenzyl fragments into
molecules of various compounds. We previously [5]
summarized methods for activation of benzyl acetate V
toward weak nucleophiles, which are based on genera-
tion of reactive intermediates, 2,6-di-tert-butyl-4-meth-
ylidenecyclohexa-2,5-dien-1-one (VI) and substituted
benzyl cation A (Scheme 2).
In the present work we synthesized sterically hin-
dered phenol derivatives on the basis of indole, trypto-
phane, and isatin. Our attempts to effect condensation
We have found that the ability of indole (I) to
undergo polymerization in acid medium [6] hampers
Scheme 1.
O
Bu-t
OH
O
O
4
6
t-Bu
Bu-t
OH
N
5
+
CH2O
+
O
N
7
Bu-t
H
II
III
IV
1797

NUGUMANOVA et al.
1798
Scheme 2.
O
t-Bu
Bu-t
Base, DMF, MeOH
–AcOH
NuH
OH
OH
CH2
t-Bu
Bu-t
t-Bu
Bu-t
VI
OH
CH2OAc
CH2Nu
t-Bu
Bu-t
H+
NuH
–H+
V
–AcOH
CH2
A
Scheme 3.
Bu-t
Bu-t
t-Bu
HO
t-Bu
O
4VI
+
OH
O
t-Bu
Bu-t
t-Bu
Bu-t
VII
VIII
its reaction with benzyl acetate V through carbocation
A. We also failed to obtain condensation product of
indole (I) with benzyl acetate V in the presence of
bases or in dipolar aprotic solvents. Presumably, the
basicity of indole (pKa –2.4 [7]) and hence its nu-
cleophilicity are insufficient for the reaction with
methylenequinone VI to occur. Under the above condi-
tions for generation of methylenequinone VI from
benzyl acetate V, the main components of the reaction
mixture were products resulting from side transforma-
tions of VI, i.e., compounds VII and VIII (Scheme 3).
quinone VI. The fraction of the latter may be con-
trolled by varying the concentration and temperature.
Raising the overall concentration decreases the equilib-
rium concentration of methylene quinone VI; there-
fore, the contribution of its dimerization and dispropor-
tionation can be reduced. In fact, when a 0.025 M
solution of benzyl acetate V and indole (I) (molar ratio
3:1) in methanol was stirred for 24 h at 50°C, we
isolated from the reaction mixture by fractional crys-
tallization 4-[3,3-bis(3,5-di-tert-butyl-4-hydroxyben-
zyl)-3H-indol-2-ylmethylidene]-2,6-di-tert-butylcyclo-
hexa-2,5-dien-1-one (IX) in 15% yield (calculated on
the initial indole) and ether X (20%, calculated on ben-
As we showed previously [8], benzyl acetate V in
alcoholic solution exists in equilibrium with methylene
Scheme 4.
OH
t-Bu
17
t-Bu
HO
Bu-t
16
15
14
13
OH
t-Bu
4
7
t-Bu
Bu-t
4a
7a
3
5
6
MeOH
2
8
V
+
+
–AcOH
9
10'
N
N
H
11'
10
11
Bu-t
I
CH2OMe
12
t-Bu
O
IX
X
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

SYNTHESIS OF STERICALLY HINDERED PHENOLIC COMPOUNDS
1799
Scheme 5.
COOH
NH2
COOH
N
H
DMSO
–AcOH
Bu-t
V
+
N
H
N
H
OH
t-Bu
XI
XII
1
groups gave cross peaks with the CH= carbon atoms,
and coupling between the CH= proton and ArCH2
methylene carbon atom was observed in the 2D
HMBC spectrum, which unambiguously indicated the
position of the sterically hindered phenol fragment in
molecule XII.
zyl acetate V) (Scheme 4). According to the H NMR
data, the tarry residue contained 10% of 2,6-di-tert-
butyl-4-methoxymethylphenol (X), traces of I and IX,
and unidentified products.
The structure of compound IX was proved by one-
and two-dimensional H and 13C NMR and IR spec-
1
1
13
Isatin II readily reacted with benzyl acetate V to
give compound IV. In this case, activation of benzyl
acetate V is achieved by carrying out the reaction in
dipolar aprotic solvents (such as DMSO) or in the
presence of acid catalysts. Taking into account that the
nucleophilicity of the NH group in molecule II is even
lower than in indole (I), we presumed that the reaction
of isatin (II) with methylene quinone VI in DMSO
begins with protonation of the carbonyl group in VI by
the acidic NH proton. It is known that benzyl acetate V
in dipolar aprotic solvents readily reacts with weak
acids, e.g., with hydrogen sulfide [5]. Substituted isatin
IV can be converted into the corresponding hydrazone
XIVa and thiosemicarbazone XIVb which attract
interest as potential polyfunctional stabilizers and bio-
logically active substances (Scheme 6). Compounds
XIVa and XIVb were synthesized by heating the re-
actants in boiling alcohol according to standard proce-
dure. When isatin (II) was treated first with phenylhy-
drazine or thiosemicarbazide and then with benzyl
acetate V, mixtures of products with different numbers
troscopy. Signals in the H and C NMR spectra were
assigned on the basis of the 2D HMBC and HSQC
spectra recorded from solutions in CDCl3, (CD3)2CO,
and C6D6. The position of the methylene quinone frag-
ment on C2 rather than on C3 followed from equiv-
alence of two ArCH2 groups in the 1H NMR (only one
AB pattern was observed; Fig. 1) and 13C NMR spectra
(δC 43.2 ppm, s) and from the absence of cross peaks
between CH= proton and C8, CH2 protons and C10, and
10(10′)-H and C3 in the 2D HMBC spectra, while
a cross peaks between 7-H and C3 was observed. Thus
the reaction of benzyl acetate V with indole (I) in
methanol results in exhaustive benzylation of the latter
and is accompanied by oxidation of the sterically hin-
dered phenol fragment in position 2 of the indole ring.
Tryptophane (XI) is a stronger nucleophile
{pKa (NH2) 9.39 [9]} than indole, and it reacted with
benzyl acetate V in DMSO under mild conditions
(Scheme 5). The structure of compound XII thus
1
13
formed was proved using two-dimensional H and C
NMR techniques. Methylene protons of the ArCH2
(a)
(b)
3.50
3.45
3.40
3.35 δ, ppm
45.0
44.0
43.0
δC, ppm
Fig. 1. Fragments of the (a) 1H and (b) 13C NMR spectra of compound IX in acetone-d6.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

NUGUMANOVA et al.
1800
Scheme 6.
RNHN
Bu-t
O
OH
IV
+
H2NNHR
N
–H2O
Bu-t
XIIIa, XIIIb
XIVa, XIVb
R = Ph (a), NH2C(S) (b).
Scheme 7.
OH
O
t-Bu
Bu-t
O
Bu-t
N
NH
II
+
OH
–H2O
NH2
O
N
N
Bu-t
H
H
XV
XVI
forms of XVI are Z and E isomers, and each isomer in
solution exists as a mixture of stereoisomers due to
restricted rotation about the C–N and N–N bonds. This
follows from the dependence of the NH signal position
in the H NMR spectra upon the concentration and
solvent polarity:
of 3,5-di-tert-butyl-4-hydroxybenzyl groups were ob-
tained, regardless on the mode of activation of benzyl
acetate V.
The reaction of isatin (II) with acylhydrazine XV
possessing a sterically hindered phenol fragment gave
acylhydrazone XVI (Scheme 7). Like compounds
XIVa and XIVb, product XVI is capable of trapping
peroxy radicals and forming complexes with metals.
1
Solvent
CDCl3 (dilute) CDCl3 (concd.) DMSO-d6
δ(=NNH), ppm
δ(NH), ppm
07.810
12.400
7.880
9.400
10.738
11.008
Acylhydrazone XVI crystallized in two forms
XVIa and XVIb having the same elemental composi-
tion but different solubilities, melting points, and Rf
values. Acylhydrazones give rise to stereoisomers due
to restricted rotation about the C–N and N–N bonds, as
well as due to Z/E isomerism with respect to the double
C=N bond [10]. Presumably, the isolated crystalline
Protons of the methylene group neighboring to the
carbonyl group resonated as two triplets corresponding
to cis (δ 3.155 ppm) and trans (δ 2.738 ppm) [11]
arrangement of the 2-(3,5-di-tert-butyl-4-hydroxy-
phenyl)ethyl substituent with respect to the C–N bond
(Fig. 2).
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Bruker MSL-400 spectrometer at 400 and 100 MHz,
respectively; the chemical shifts were measured rela-
tive to the corresponding solvent signals. The IR spec-
tra were obtained on a Bruker Vector-22 spectrometer
with Fourier transform at a resolution of 1 cm–1.
1-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2,3-dihy-
dro-1H-indole-2,3-dione (IV). a. A solution of 1.47 g
(0.01 mol) of isatin (II), 2.06 g (0.01 mol) of 2,6-di-
tert-butylphenol (III), and 1.5 ml of a 33% formalde-
hyde solution in 15 ml of ethanol was heated for 20 h
3.4
3.2
3.0
2.8
2.6 δ, ppm
1
Fig. 2. A fragment of the H NMR spectrum of N′-(2-oxo-
2,3-dihydro-1H-indol-3-ylidene)-3-(3,5-di-tert-butyl-4-hy-
droxyphenyl)propionohydrazide (XVIb) in CDCl3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

SYNTHESIS OF STERICALLY HINDERED PHENOLIC COMPOUNDS
1801
under reflux with stirring. The mixture was cooled to
room temperature, poured into 150 ml of water, and
extracted with methylene chloride. The extract was
dried over MgSO4, and the solvent was distilled off
under reduced pressure to obtain 2.9 g (83%) of a dark
red tarry material containing 7% of compound IV
(according to the 1H NMR data).
(4H, CH2, 2J = 14.0 Hz), 5.68 s (2H, OH), 6.57 s (4H,
3
15-H), 7.28 d (1H, 7-H, J = 7.7 Hz), 7.31 t.d (1H,
3
4
4
6-H, J = 7.7, J = 1.0 Hz), 7.40 d (1H, 10-H, J =
3
4
2.0 Hz), 7.42 t.d (1H, 5-H, J = 7.7, J = 1.0 Hz),
7.50 s (1H, 8-H), 7.69 d (1H, 4-H, 3J = 7.7 Hz), 8.66 d
(1H, 10′-H, J = 2.0 Hz). 13C NMR spectrum (ace-
4
tone-d6), δC, ppm: 30.03 (CMe3), 30.19 (CMe3), 30.74
(CMe3), 34.99 s (CMe3), 36.00 s (CMe3), 36.33 s
b. A solution of 1.47 g (0.01 mol) of isatin (II) and
2.78 g (0.01 mol) of 3,5-di-tert-butyl-4-hydroxybenzyl
acetate (V) in 25 ml of DMF was stirred for 3 h at
70°C. The mixture was cooled to room temperature,
and the precipitate was filtered off, washed with water,
and dried in air until constant weight. Yield 1.32 g
(36%). From the filtrate we isolated an additional
portion of compound IV, 1.91 g (52%), orange crys-
tals, mp 245–246°C (from acetone). 1H NMR spectrum
(CDCl3), δ, ppm: 1.40 s (18H, CMe3), 4.81 s (2H,
1
(CMe3), 43.25 t (CH2, J = 129.0 Hz), 67.13 s (C3),
1
3
122.26 d.d (C7, J = 161.0, J = 8.4 Hz), 124.63 d.d
(C4, J = 159.0, J = 7.5 Hz), 126.90 d (C6, J =
1
3
1
155.0 Hz), 126.90 d (C15, 1J = 155.0 Hz), 128.01 t (C14,
2J = 5.0 Hz), 128.78 d.d (C5, J = 161.0, J = 7.8 Hz),
1
3
1
1
131.48 d (C10′, J = 164.0 Hz), 131.73 d (C8, J =
153.0 Hz), 136.34 d (C10, J = 159.0 Hz), 137.12 s
1
(C16), 137.71 s (C9), 143.11 s (C3a), 149.51 s (C11),
150.67 s (C11′), 153.37 t (C17, J = 8.7 Hz), 158.12 s
3
(C7a), 180.44 s (C2), 187.78 t (C12, 3J = 9.0 Hz). Found,
%: C 83.1; H 9.47; N 1.83. C53H71NO3. Calculated, %:
C 82.71; H 9.23; N 1.82.
3
CH2), 5.23 s (1H, OH), 6.91 d (1H, 7-H, J = 7.5 Hz),
7.09 t (1H, 5-H, 3J = 7.2 Hz), 7.16 s (2H, Harom), 7.55 t
3
3
(1H, 6-H, J = 7.5 Hz), 7.59 d (1H, 4-H, J = 7.2 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 30.45 (CMe3);
34.54 (CMe3); 44.61 (CH2); 111.18, 118.02, 123.83,
124.90, 125.51, 125.61, 136.86, 138.33, 151.45,
153.89 (Carom); 158.50 (NC=O); 183.74 (C=O). Found,
%: C 75.99; H 7.57; N 3.54. C23H27NO3. Calculated,
%: C 75.62; H 7.40; N 3.82.
The filtrate was evaporated by half and poured into
300 ml of water. The precipitate was filtered off,
washed with water, dried in air until constant weight,
and washed with hexane to isolate 1.53 g (20%) of
2,6-di-tert-butyl-4-methoxymethylphenol (X) as a light
1
brown powder with mp 100–101°C. H NMR spec-
trum (CDCl3), δ, ppm: 1.44 s (18H, CMe3), 3.39 s (3H,
OCH3), 4.34 s (2H, CH2), 5.17 s (1H, OH), 7.13 s
(2H, Harom). The hexane filtrate was evaporated under
reduced pressure. The residue was a dark orange tarry
c. A solution of 1.47 g (0.01 mol) of isatin (II) and
2.78 g (0.01 mol) of 3,5-di-tert-butyl-4-hydroxybenzyl
acetate (V) in a mixture of 15 ml of formic acid and
15 ml of acetone was stirred for 20 h at 70°C. The
mixture was cooled to room temperature, and the pre-
cipitate was filtered off, washed with water, and dried
in air until constant weight. Yield 1.47 g (40%), orange
crystals. From the filtrate we isolated an additional
portion, 1.6 g (44%), of a red tarry substance which
contained 20% of compound IV (according to the
1H NMR data).
1
material containing (according to the H NMR data)
10% of ether X, traces of compounds I and IX, and
unidentified products.
2-(3,5-Di-tert-butyl-4-hydroxybenzylamino)-3-
(1H-indol-3-yl)propionic acid (XII). A solution of
2.04 g (0.01 mol) of tryptophane (XI) and 2.78 g
(0.01 mol) of compound V in 60 ml of DMSO was
stirred for 3 h at 70°C. The mixture was treated with
200 ml of a 10% aqueous solution of sodium chloride,
and the precipitate was filtered off, washed with water,
and dried in air until constant weight. Yield 4.09 g
(97%), colorless powder. 1H NMR spectrum (CD3OD),
δ, ppm: 1.36 s (18H, CMe3), 3.20–3.25 d.d (1H,
4-[3,3-Bis(3,5-di-tert-butyl-4-hydroxybenzyl)-3H-
indol-2-ylmethylidene]-2,6-di-tert-butylcyclohexa-
2,5-dien-1-one (IX). A solution of 1.17 g (0.01 mol) of
indole (I) and 8.34 g (0.03 mol) of compound V in
300 ml of methanol was stirred for 24 h at 50°C. The
mixture was cooled to room temperature, and the pre-
cipitate was filtered off, washed with a small amount
of methanol, and dried in air until constant weight.
Yield 1.15 g (15%), yellow–orange crystals, mp 195–
197°C. IR spectrum, ν, cm–1: 3623 (OH), 1613 (C=O).
1H NMR spectrum (acetone-d6), δ, ppm: 1.17 s (36H,
CMe3), 1.23 s (9H, CMe3), 1.37 s (9H, CMe3), 3.42 d.d
2
3
3-CH2, J = 15.3, J = 8.8 Hz), 3.45–3.52 d.d (1H,
2
3
3-CH2, J = 15.3, J = 4.6 Hz), 3.77–3.82 d.d (1H,
3
3
CHCO, J = 8.8, J = 4.6 Hz), 3.93 s (2H, NCH2),
3
7.02 t (1H, 5-H, J = 8.2 Hz), 7.03 s (2H, o-H), 7.12 t
(1H, 6-H, J = 8.2 Hz), 7.18 s (1H, 2-H), 7.37 d (1H,
7-H, J = 8.2 Hz), 7.60 d (1H, 4-H, J = 8.2 Hz).
13C NMR spectrum (CD3OD), δC, ppm: 28.00 (CH2);
3
3
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

NUGUMANOVA et al.
1802
N′-(2-Oxo-2,3-dihydro-1H-indol-3-ylidene)-3-
(3,5-di-tert-butyl-4-hydroxyphenyl)propionohydra-
zide (XVIa, XVIb). A solution of 1.47 g (0.01 mol) of
isatin (II) and 2.92 g (0.01 mol) of 3-(3,5-di-tert-butyl-
4-hydroxyphenyl)propionohydrazide (XV) in 50 ml of
ethanol was heated for 4 h under reflux. The mixture
was cooled to room temperature, and the precipitate
was filtered off, washed with ethanol, and dried in air
until constant weight. Yield of XVIa 2.56 g (61%),
yellow crystals, mp 214–216°C (from acetonitrile).
1H NMR spectrum (CDCl3), δ, ppm: 1.45 s (18H,
CMe3), 2.30 t (2H, CH2Ar, 3J = 7.8 Hz), 3.21 br.t (2H,
30.59 (CMe3); 35.51 (CMe3); 51.87 (CH2N); 62.50
(CHN); 109.33 (C3); 125.14 (C2); 112.53, 119.33,
120.33, 122.87, 123.27, 127.38, 128.39, 138.34, 139.79,
156.27 (Carom); 173.67 (C=O). Found, %: C 74.15;
H 8.21; N 6.52. C26H34N2O3. Calculated, %: C 73.93;
H 8.06; N 6.64.
1-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2,3-di-
hydro-1H-indole-2,3-dione 3-(phenylhydrazone)
(XIVa). A solution of 3.65 g (0.01 mol) of compound
IV, 1.55 g (0.012 mol) of phenylhydrazine (XIIIa)
hydrochloride, and 1.68 ml (0.012 mol) of triethyl-
amine in 50 ml of ethanol was heated for 4 h under
reflux with stirring. The mixture was cooled to room
temperature, and the precipitate was filtered off,
washed with ethanol, and dried in air until constant
weight. Yield 3.89 g (85%), yellow crystals, mp 203–
3
CH2CO), 5.07 s (1H, OH), 6.97 d (1H, 7-H, J =
3
7.7 Hz), 7.08 s (2H, o-H), 7.14 t (1H, 5-H, J =
3
7.6 Hz), 7.41 t (1H, 6-H, J = 7.7 Hz), 7.64 br.s (1H,
4-H), 7.88 s (1H, NH), 9.40 s (1H, =NNH). Found, %:
C 71.58; H 7.60; N 9.64. C25H31N3O3. Calculated, %:
C 71.26; H 7.36; N 9.98.
1
205°C. H NMR spectrum (CDCl3), δ, ppm: 1.41 s
(18H, CMe3), 4.90 s (2H, CH2), 5.19 s (1H, OH),
From the filtrate we isolated 0.7 g (17%) of yellow
compound XVIb, mp 223–224°C (from acetonitrile).
1H NMR spectrum (CDCl3), δ, ppm: 1.47 s (18H,
CMe3); 2.74 br.t (0.5H, CH2CO); 3.01 t (2H, CH2Ar,
3J = 7.8 Hz); 3.16 t (1.5H, CH2CO, 3J = 7.8 Hz); 5.09 s
3
6.92 d (1H, 7-H, J = 8.0 Hz), 7.00–7.50 m (7H,
3
Harom), 7.17 s (2H, Harom), 7.67 d (1H, 4-H, J =
8.0 Hz), 12.85 s (1H, NH). 13C NMR spectrum
(CDCl3), δC, ppm: 30.49 (CMe3); 34.55 (CMe3); 43.75
(CH2); 109.62, 114.61, 119.12, 121.69, 123.38, 124.68,
126.82, 127.29, 128.12, 129.66, 136.55, 140.87, 142.98
(Carom); 153.58 (C=N); 162.47 (C=O). Found, %:
C 76.87; H 7.50; N 8.89. C29H33N3O2. Calculated, %:
C 76.48; H 7.25; N 9.23.
3
(1H, OH); 6.94 d (1H, 7-H, J = 7.8 Hz); 7.03–7.16 m
(3H, o-H, 5-H); 7.35 t (1H, 6-H, 3J = 7.8 Hz); 7.60 d
3
(1H, 4-H, J = 7.3 Hz); 7.80 s, 7.90 s, and 8.13 s (1H,
NH); 12.40 s and 12.95 s (1H, =NNH). 13C NMR spec-
trum (CDCl3), δC, ppm: 30.35 (CMe3); 30.50 (CH2Ar);
34.32 (CMe3); 34.52 (CH2CO); 111.00, 120.59, 120.82,
123.20, 124.89, 131.13, 131.52, 132.91, 136.12, 140.93
(Carom); 152.19 (C=N); 162.62 (C2=O); 175.79 (C=O).
Found, %: C 71.44; H 7.58; N 9.68. C25H31N3O3. Cal-
culated, %: C 71.26; H 7.36; N 9.98.
1-(3,5-Di-tert-butyl-4-hydroxybenzyl)-2,3-di-
hydro-1H-indole-2,3-dione 3-(thiosemicarbazone)
(XIVb). A solution of 3.65 g (0.01 mol) of compound
IV, 1.53 g (0.012 mol) of thiosemicarbazide (XIIIb)
hydrochloride, and 1.68 ml (0.012 mol) of triethyl-
amine in 50 ml of ethanol was stirred for 4 h on
heating under reflux. The mixture was cooled to room
temperature, and the precipitate was filtered off,
washed with ethanol, and dried in air until constant
weight. Yield 2.65 g (60%), yellow crystals, mp 235°C
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1
(decomp.). H NMR spectrum (benzene-d6), δ, ppm:
1.40 s (18H, CMe3), 4.96 s (2H, CH2), 6.11 s (1H,
3
OH), 7.13 t (1H, 5-H, J = 7.3 Hz), 7.17 d (1H, 7-H,
3
3J = 7.9 Hz), 7.30 s (2H, o-H), 7.40 t (1H, 6-H, J =
3
7.9 Hz), 7.71 d (1H, 4-H, J = 7.3 Hz), 8.17 s (1H,
NH2), 8.44 s (1H, NH2), 11.62 s (1H, NH). 13C NMR
spectrum (CDCl3), δC, ppm: 30.45 (CMe3); 34.54
(CMe3); 44.19 (CH2); 110.38, 119.71, 121.09, 123.37,
124.99, 125.92, 128.57, 131.69, 136.71, 143.85 (Carom);
153.84 (C=N); 161.27 (C=O); 180.36 (C=S). Found,
%: C 66.01; H 6.99; N 12.48. C24H30N4O2S. Calculat-
ed, %: C 65.75; H 6.85; N 12.78.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007

SYNTHESIS OF STERICALLY HINDERED PHENOLIC COMPOUNDS
1803
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 12 2007